Homeobox genes, encoding transcriptional regulators, act in complex regulatory cascades to control the coordinated expression of genes involved in specific developmental processes. Originally identified and studied in Drosophila, homeobox genes have now been isolated from a variety of vertebrate species, including human. We have asked the question whether specific homeobox genes may control the coordinated expression of genes involved in human cellular transformation and in tumor invasion and metastasis. We have targeted human breast cancer as an initial model system. We have taken advantage of the fact that all known homeobox genes in all species share a common 180 bp segment of DNA that encodes a highly conserved 60 amino acid domain responsible for binding to DNA. Using degenerate primers within this common DNA segment and polymerase chain reaction technology, we amplified homeobox gene segments from RNA that had been extracted from a variety of human breast cancer cell lines. We identified unique homeobox sequences that are not present in the Genebank. Current efforts are directed toward isolating full length cDNA clones of these unique genes to determine their complete sequences and regulatory functions in breast cancer.